{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:44:25Z","timestamp":1790905465029,"version":"4.1.0"},"reference-count":76,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T00:00:00Z","timestamp":1551225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["603019"],"award-info":[{"award-number":["603019"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Women with atypical squamous cells of undetermined significance (ASC\u2010US) can be triaged accurately with a high\u2010risk human papillomavirus (hrHPV) test to identify those who need a referral. However, the triage of low\u2010grade squamous intraepithelial lesion (LSIL) with hrHPV testing has very low specificity. Overexpression of p16, with or without Ki\u201067, indicates neoplastic transformation of human papillomavirus\u2013infected cervical cells and may more accurately predict underlying cervical intraepithelial neoplasia of grade 3 or worse (CIN3+).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A literature search was conducted in 3 bibliographic databases. Studies were selected if they included women with ASC\u2010US or LSIL who were triaged with dual staining (p16\/Ki\u201067) and\/or p16 staining and, if available, with a comparator hrHPV test to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or CIN3+.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010eight studies were eligible. The sensitivity of p16 staining for CIN3+ was significantly lower than that of hrHPV DNA testing (ratio for ASC\u2010US, 0.87; 95% confidence interval [CI], 0.78\u20100.97; ratio for LSIL, 0.86; 95% CI, 0.80\u20100.93). In contrast, the specificity of p16 staining was substantially higher with relative specificities of 1.60 (95% CI, 1.35\u20101.88) and 2.29 (95% CI, 2.05\u20102.56) for ASC\u2010US and LSIL respectively. Dual staining was as sensitive as hrHPV DNA testing but was more specific (ratio for ASC\u2010US, 1.65; 95% CI, 1.42\u20101.92; ratio for LSIL, 2.45; 95% CI, 2.17\u20102.77).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This meta\u2010analysis confirms that p16 staining and p16\/Ki\u201067 staining are more specific for CIN2+\/CIN3+ than hrHPV DNA testing. Although p16 staining is less sensitive for CIN3+ than hrHPV DNA testing, dual staining has similar sensitivity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22103","type":"journal-article","created":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T13:14:46Z","timestamp":1551273286000},"page":"169-180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Meta\u2010analysis of the accuracy of p16 or p16\/Ki\u201067 immunocytochemistry versus HPV testing for the detection of CIN2+\/CIN3+ in triage of women with minor abnormal cytology"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8728-2175","authenticated-orcid":false,"given":"Eliana","family":"Peeters","sequence":"first","affiliation":[{"name":"Unit of Cancer Epidemiology Belgian Cancer Centre, Sciensano Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1251-0836","authenticated-orcid":false,"given":"Nicolas","family":"Wentzensen","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bergeron","sequence":"additional","affiliation":[{"name":"Laboratoire Cerba Cergy Pontoise France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Arbyn","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology Belgian Cancer Centre, Sciensano Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.04.015"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-0306"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.06.095"},{"key":"e_1_2_8_5_1","first-page":"1","article-title":"Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions","volume":"3","author":"Arbyn M","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp471"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2007.07.050"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(16)32441-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35096061"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1523"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1174"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.2002.01359.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2006.01.052"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2005.37.6.319"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/10520290310001659466"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21378"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9"},{"key":"e_1_2_8_18_1","first-page":"867","article-title":"Immunobiochemical and molecular biologic characterization of the cell proliferation\u2013associated nuclear antigen that is defined by monoclonal antibody Ki\u201067","volume":"138","author":"Gerdes J","year":"1991","journal-title":"Am J Pathol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21205"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.LGT200570"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8307"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0270"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2010.956920"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181e8b2c4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPXSVCDZ3D5MZM"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22420"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4178\/epih\/e2014016"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.13076"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2008.10.005"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-3-25"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X0900900203"},{"key":"e_1_2_8_32_1","unstructured":"TakwoingiY DeeksJ.MetaDAS: a SAS macro for meta\u2010analysis of diagnostic accuracy studies. 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